Identification of a Prognostic Immune Signature for Esophageal Squamous Cell Carcinoma to Predict Survival and Inflammatory Landscapes.

Chaoqi Zhang,Zhihui Zhang,Yuejun Luo,Feng Wang,Nan Sun,Lingling Fang,Jie He,Yun Che,Guochao Zhang,Yi Zhang,Zhen Zhang

doi:10.3389/fcell.2020.580005

Abstract

Immunotherapy has achieved success in the treatment of esophageal squamous cell carcinoma (ESCC). However, studies concerning immune phenotypes within the ESCC microenvironment and their relationship with prognostic outcomes are limited. We constructed and validated an individual immune-related risk signature for patients with ESCC. We collected 196 ESCC cases, including 119 samples from our previous public data (GSE53624) to use as a training set and an independent cohort with 77 quantitative real-time polymerase chain reaction (qRT-PCR) data, which we used for validation. Head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma (LUSC) cohorts were also collected for validation. A least absolute shrinkage and selection operator (LASSO) model and a stepwise Cox proportional hazards regression model were used to construct the immune-specific signature. The potential mechanism and inflammatory landscapes of the signature were explored using bioinformatics and immunofluorescence assay methods. This signature predicted different prognoses in clinical subgroups and the independent cohort, as well as in patients with HNSCC and LUSC. Further exploration revealed that the signature was associated with specific inflammatory activities (activation of macrophages and T-cell signaling transduction). Additionally, high-risk patients exhibited distinctive immune checkpoints panel and higher regulatory T cell and fibroblast infiltration. This signature served as an independent prognostic factor in ESCC. This was the first applicable immune-related risk signature for ESCC. Our results furnished new hints of immune profiling of ESCC, which may provide some clues to further optimize associated cancer immunotherapies.

Highlights

As reported by global cancer statistics in 2018, esophageal cancer (EC) is the sixth leading cause of cancer deaths and the seventh most common cancer worldwide (Bray et al, 2018), with an estimated 70% of EC cases occurring in China (Chen et al, 2019; Yin et al, 2020)
A total of 119 patients with esophageal squamous cell carcinoma (ESCC) with clinical data from GSE53624 were included as the training cohort, and the demographics of the cohort are listed in Supplementary Table 2
The univariate Cox proportional regression analysis showed that 16 immune-related genes were statistically associated with overall survival (OS) (P < 0.01) (Supplementary Table 3)

Summary

Introduction

As reported by global cancer statistics in 2018, esophageal cancer (EC) is the sixth leading cause of cancer deaths and the seventh most common cancer worldwide (Bray et al, 2018), with an estimated 70% of EC cases occurring in China (Chen et al, 2019; Yin et al, 2020). Neoadjuvant chemoradiotherapy followed by resection has moderately improved the prognosis of patients with locally advanced ESCC compared to traditional surgery alone (Allum et al, 2011; Shapiro et al, 2015). Owing to their high heterogeneity, patients with ESCC tend to exhibit individual differences in therapeutic efficacy, even under the same clinical guidelines and recommended treatment. This may prevent clinical practices from being able to precisely stratify patients with ESCC, leading to the predicament of depersonalized, and often suboptimal treatment.

Methods

Results

Conclusion